1. Field of the Invention
This invention is related to heterocyclic bispyridines, pharmaceutical compositions containing them and methods of using them to treat neurological disorders in mammals.
2. State of the Art
Alzheimer's Disease (AD) and Senile Dementia (SD) are neurological disorders generally characterized by a reduction in cortical cholinergic activity. Neurological disorders may be characterized by altered neurotransmitter function and concomitant cognitive impairment in diseases such as, but not limited to, Alzheimer's Disease, Parkinson's Disease, Pick's Disease, Huntington's Disease, and Age Associated Memory Impairment. This has led to a focus on the basal forebrain cholinergic system as the major source of neurochemical and neuroanatomical substrates mediating age-related memory loss. However, it is very unlikely, given the complexity of the brain, that any single neurotransmitter would selectively and exclusively be involved in a neurological disorder so pervasive as dementia or age-related memory impairment. A growing literature has described multiple neurotransmitter, neuroanatomical and behavioral changes in dementia from varying etiologies. It is, therefore, possible and likely that age-related memory deficits and cognitive impairment resulting from AD and SD involve concurrent changes in several neurotransmitter systems and neurotransmitter replacement therapy should involve multiple systems in the brain.
U.S. Pat. Nos. 4,760,083, issued Jul. 26, 1988, 5,173,489, issued Dec. 22, 1992 all herein incorporated by reference, describe many compounds useful in the treatment of neurological disorders such as Alzheimer's Disease and Senile Dementia. In U.S. Pat. No. 5,173,489, certain thiophene heterocycles, pyrrolo and pyrazole heterocycles are disclosed. While the compounds of the present, invention are similar to, those within the broad scope of application U.S. Pat. No. 5,173,489 issued Dec. 22, 1992, there is no suggestion in that application that the compounds of the present invention have superior neurotransmitter releasing profiles, as measured in an in vitro release, or an unexpectedly good dosage profile as measured by hypoxia-induced cognition impairment.